The effects of REM sleep-inhibiting drugs in neonatal rats: evidence for a distinction between neonatal active sleep and REM sleep.
Neonatal active sleep (AS) has been considered to be homologous and continuous with rapid-eye-movement (REM) sleep in adult animals. We have recently proposed an alternative view that AS is an undifferentiated sleep state distinct from REM sleep. To test these opposing views on the relationship of AS and REM sleep, neonatal rats (P11, P14 and P20) were systemically injected with compounds that inhibit REM sleep in adults. Zimelidine (ZMI) and desipramine (DMI) are monoamine uptake inhibitors which increase synaptic concentrations of serotonin and norepinephrine, respectively. Serotonin and norepinephrine inhibit brainstem cholinergic neurons important in REM sleep generation. Atropine (ATR) is a muscarinic receptor antagonist that blocks the post-synaptic effects of cholinergic projections. Only DMI (5 mg/kg) suppressed AS at P11. ZMI (6 mg/kg) and ATR (6 mg/kg) did not suppress AS until P14. These data suggest that serotonergic and cholinergic regulation of AS are absent before P14. The fact that AS in P11 rats is not affected by cholinergic antagonists supports the hypothesis that AS and REM sleep represent different sleep states.
Frank
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MG
Biological Sciences, Stanford University, CA 94305, USA. mgf@phy.ucsf.edu
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Heller
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D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000187:drug effects; D001285:Atropine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004569:Electroencephalography; D004576:Electromyography; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D015031:Zimeldine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D001285:Atropine; D003891:Desipramine; D018727:Muscarinic Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D015031:Zimeldine